Molecule Information

General Information of the Molecule (ID: Mol01823)

• Name: Myeloid cell surface antigen CD33 (CD33) ,Homo sapiens
• Synonyms: Sialic acid-binding Ig-like lectin 3; Siglec-3; gp67; CD antigen CD33; SIGLEC3
• Molecule Type: Protein
• Gene Name: CD33
• Gene ID: 945
• Location: chr19:51,225,064-51,243,860[+]
• Sequence:
  MPLLLLLPLLWAGALAMDPNFWLQVQESVTVQEGLCVLVPCTFFHPIPYYDKNSPVHGYW
  FREGAIISRDSPVATNKLDQEVQEETQGRFRLLGDPSRNNCSLSIVDARRRDNGSYFFRM
  ERGSTKYSYKSPQLSVHVTDLTHRPKILIPGTLEPGHSKNLTCSVSWACEQGTPPIFSWL
  SAAPTSLGPRTTHSSVLIITPRPQDHGTNLTCQVKFAGAGVTTERTIQLNVTYVPQNPTT
  GIFPGDGSGKQETRAGVVHGAIGGAGVTALLALCLCLIFFIVKTHRRKAARTAVGRNDTH
  PTTGSASPKHQKKSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNPSKDTSTEYSE
  VRTQ
• Function: Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state. Preferentially recognizes and binds alpha-2,3- and more avidly alpha-2,6-linked sialic acid-bearing glycans. Upon engagement of ligands such as C1q or syalylated glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in CD33 cytoplasmic tail are phosphorylated by Src-like kinases such as LCK. These phosphorylations provide docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. In turn, these phosphatases regulate downstream pathways through dephosphorylation of signaling molecules. One of the repressive effect of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K.
• Uniprot ID: CD33_HUMAN
• Ensembl ID: ENSG00000105383
• HGNC ID: HGNC:1659

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Gemtuzumab ozogamicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Acute myeloid leukemia [1]

• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Resistant Drug: Gemtuzumab ozogamicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: U937 cells; Blood; Homo sapiens (Human); CVCL_0007
• In Vitro Model: KG-1 cells; Bone marrow; Homo sapiens (Human); CVCL_0374
• In Vitro Model: GDM-1 cells; Blood; Homo sapiens (Human); CVCL_1230
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: NB4 cells; Bone marrow; Homo sapiens (Human); CVCL_0005
• In Vitro Model: TF-1 cells; Blood; Homo sapiens (Human); CVCL_0559
• Experiment for Molecule Alteration: Western Blot Analysis
• Experiment for Drug Resistance: Flow cytometric SCNP assays
• Mechanism Description: AKT signaling modulates GO/calicheamicin-gamma1 cytotoxicity and is associated with cellular-resistance to these drugs. In turn, inhibition of AKT activation can greatly increase GO/calicheamicin-gamma1 sensitivity.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Acute myeloid leukemia [ICD-11: 2A60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bone marrow
• The Specified Disease: Acute myeloid leukemia
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.37E-13; Fold-change: 5.78E-01; Z-score: 1.13E+00

References

• Ref 1: AKT signaling as a novel factor associated with in vitro resistance of human AML to gemtuzumab ozogamicin PLoS One. 2013;8(1):e53518. doi: 10.1371/journal.pone.0053518. Epub 2013 Jan 8.